PROJECT SUMMARY There is a timely and urgent need to understand and leverage the context of lung cancer screening to deliver smoking cessation treatment and promote cessation among individuals at high risk for lung and other smoking- related diseases. The long-term goal is to maximize the public health benefits of lung cancer screening by providing a blueprint of best practices for integrating and sustaining tobacco treatment delivery in lung cancer screening settings. The current project will make a vital contribution by identifying superior and scalable tobacco treatment components with relevance for current smokers seeking screening that can be cost- effectively delivered with high implementation fidelity by heterogeneous lung cancer screening sites. The proposed research will use an innovative methodological framework, the Multiphase Optimization Strategy (MOST), to design an optimized, scalable evidence-based tobacco treatment package that can be readily integrated within lung cancer screening sites. MOST involves highly efficient, randomized experimentation to precisely quantify the effects of individual treatment components and identify synergistic effects by combining them into an effective tobacco treatment package. This information then guides assembly of an optimized treatment package that achieves target outcomes with minimal resource consumption and staff burden. The rationale for the proposed research is that once an optimized tobacco treatment package is established, future comparative effectiveness trials can examine strategies for wider implementation and dissemination in LDCT- LCS settings. In partnership with the Lung Cancer Alliance and their National Framework for Excellence in Lung Cancer Screening, we will identify 18 heterogeneous lung cancer screening sites across the United States that will serve as demonstration field sites. Sixty current smokers will be recruited from each of the 18 participating screening sites (n=1,080). The findings will guide assembly of an optimized and scalable cessation treatment package that achieves superior cessation outcomes with attention to minimizing burden in lung cancer screening sites. This study will apply MOST to achieve the following aims: Aim 1: To use a highly efficient MOST to identify which of four evidence-based tobacco treatment components under consideration contribute to superior cessation endpoints. The four tobacco treatment components to be tested are: (1) Motivational Interviewing (MI) (Yes vs. No); (2) NRT Patch (Yes vs. No); 3) NRT Lozenge (Yes vs No); and 4) Message Framing (Gain vs Loss); Aim 2: To estimate the cost and incremental cost-effectiveness of evidence- based tobacco treatment components, delivered alone and in combination; Aim 3: Guided by well-established evaluation and conceptual implementation science frameworks, we will conduct a robust, mixed methods evaluation of the implementation process and assess factors that may influence implementation and sustainability for delivering and disseminating effective models for smoking cessation treatment in lung cancer screening settings.